Protection of cardiac myocytes via delta(1)-opioid receptors, protein kinase C, and mitochondrial K(ATP) channels. Am J Physiol Heart Circ Physiol 2001 Jan;280(1):H377-83
Date
12/21/2000Pubmed ID
11123254DOI
10.1152/ajpheart.2001.280.1.H377Scopus ID
2-s2.0-0035001955 (requires institutional sign-in at Scopus site) 74 CitationsAbstract
The objective of the present study was to investigate the role of delta(1)-opioid receptors in mediating cardioprotection in isolated chick cardiac myocytes and to investigate whether protein kinase C and mitochondrial ATP-sensitive K(+) (K(ATP)) channels act downstream of the delta(1)-opioid receptor in mediating this beneficial effect. A 5-min preexposure to the selective delta(1)-opioid receptor agonist (-)-TAN-67 (1 microM) resulted in less myocyte injury during the subsequent prolonged ischemia compared with untreated myocytes. 7-Benzylidenenaltrexone, a selective delta(1)-opioid receptor antagonist, completely blocked the cardioprotective effect of (-)-TAN-67. Naltriben methanesulfonate, a selective delta(2)-opioid receptor antagonist, had only a slight inhibitory effect on (-)-TAN-67-mediated cardioprotection. Nor-binaltorphimine dihydrochloride, a kappa-opioid receptor antagonist, did not affect (-)-TAN-67-mediated cardioprotection. The protein kinase C inhibitor chelerythrine and the K(ATP) channel inhibitors glibenclamide, a nonselective K(ATP) antagonist, and 5-hydroxydecanoic acid, a mitochondrial selective K(ATP) antagonist, reversed the cardioprotective effect of (-)-TAN-67. These results suggest that the delta(1)-opioid receptor is present on cardiac myocytes and mediates a potent cardioprotective effect via protein kinase C and the mitochondrial K(ATP) channel.
Author List
Huh J, Gross GJ, Nagase H, Liang BTMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAlkaloids
Animals
Benzophenanthridines
Benzylidene Compounds
Cells, Cultured
Chick Embryo
Enzyme Inhibitors
Glyburide
Heart
Ischemia
Ischemic Preconditioning, Myocardial
Mitochondria, Heart
Myocardium
Naltrexone
Narcotic Antagonists
Phenanthridines
Potassium Channel Blockers
Protein Kinase C
Quinolines
